The mechanisms underlying decreased performance of chronically implanted biomedical devices will be investigated. Microelectrode arrays will be implanted into the auditory cortex of adult rats. Electrophysiological recordings will be performed to measure electrode impedance and record evoked single unit activity. Animals will be sacrificed from 3 to 28 days post-implant and immunohistochemical methods applied. The adsorbed cell types on retrieved microelectrodes will be evaluated. Changes in electrical impedance and recording activity will be correlated with tissue response. The objective is to determine how microglial ceils and astrocytic components contribute to increasing electrical impedance and loss of single unit recording with recording electrodes. (2) The impedance of microelectrodes will be characterized in vitro based on adsorbing species availability. After baseline characterization, extracellular molecules will be added to the media including proteins and ceils (reactive microglia, astrocytes, and fibroblasts) and characterization will continue. Cultures will be fixed at various times and examined using indirect immunohistochemistry and cell type specific markers. Changes in impedance will be correlated with adsorbing species and the extent of cell colonization. (3) A resting 3-D culture model of cortical brain tissue will be created using mixed primary cells suspended in an extracellular matrix gel. Serum treated probes will be implanted, and the response evaluated using microscopic methods and indirect immunohistochemistry. The ability to detect sequential changes in microglial activation will be evaluated. The long-term objective of this project is to formulate approaches to abnormality and to better understand the wound healing response in brain.